ArticleThe Journal of biological chemistry2012
Substrate specificity of the two mitochondrial ornithine carriers can be swapped by single mutation in substrate binding site.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.Orphanet journal of rare diseases · 2015Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Evolutionary history and recombination in the mitochondrial carrier SLC25 superfamily analyzed by similarities in the exon and transmembrane α-helix sequences.Protein science : a publication of the Protein Society · 2026Article
- The peculiar properties of mitochondrial carriers of the SLC25 family.The Biochemical journal · 2025Review
- FAHD1 and mitochondrial metabolism: a decade of pioneering discoveries.The FEBS journal · 2025Review
- Review
- Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome in Vietnamese Patients.Medicina (Kaunas, Lithuania) · 2024Article
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- Layered mechanisms regulating the human mitochondrial NAD+ transporter SLC25A51.Biochemical Society transactions · 2023Review
- Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.Biomolecules · 2023Article
- New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions.Molecular biology and evolution · 2023Article
- Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NADIUBMB life · 2022Review
- Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS.Nature communications · 2022Article
- Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins.International journal of molecular sciences · 2022Article
- Immune Alterations in a Patient With Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome: A Case Report.Frontiers in immunology · 2022Article
- Learning from Yeast about Mitochondrial Carriers.Microorganisms · 2021Review
- The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs.Biomolecules · 2021Review
- Structural determinants of ligands recognition by the human mitochondrial basic amino acids transporter SLC25A29. Insights from molecular dynamics simulations of the c-state.Computational and structural biotechnology journal · 2021Article
- The SLC25 Carrier Family: Important Transport Proteins in Mitochondrial Physiology and Pathology.Physiology (Bethesda, Md.) · 2020Review
- Diseases Caused by Mutations in Mitochondrial Carrier GenesBiomolecules · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial carriers are a large family of proteins that transport specific metabolites across the inner mitochondrial membrane. Sequence and structure analysis has indicated that these transporters have substrate binding sites in a similar location of the central cavity consisting of three major contact points. Here we have characterized mutations of the proposed substrate binding site in the human ornithine carriers ORC1 and ORC2 by carrying out transport assays with a set of different substrates. The different substrate specificities of the two isoforms, which share 87% identical amino acids, were essentially swapped by exchanging a single residue located at position 179 that is arginine in ORC1 and glutamine in ORC2. Altogether the substrate specificity changes demonstrate that Arg-179 and Glu-180 of contact point II bind the C(α) carboxylate and amino group of the substrates, respectively. Residue Glu-77 of contact point I most likely interacts with the terminal amino group of the substrate side chain. Furthermore, it is likely that all three contact points are involved in the substrate-induced conformational changes required for substrate translocation because Arg-179 is probably connected with Arg-275 of contact point III through Trp-224 by cation-π interactions. Mutations at position 179 also affected the turnover number of the ornithine carrier severely, implying that substrate binding to residue 179 is a rate-limiting step of the catalytic transport cycle. Given that Arg-179 is located in the vicinity of the matrix gate, it is concluded that it is a key residue in the opening of the carrier to the matrix side.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.